Erythrocyte sedimentation rate (ESR) is one of the traditional tests performed on whole blood in hematology laboratories. ESR measures the distance red blood cells sediment, or fall, in a vertical tube over a given period of time. The measurement of sedimentation is calculated as millimeters of sedimentation per hour. It takes more than one hour to complete and typically requires a significant blood volume (˜mL).
Hematocrit (HCT) or packed red blood cell volume is the ratio of the volume of red blood cells (expressed as percentage or as a decimal fraction) to the volume of whole blood of which the red blood cells are a component. In micromethods for determining hematocrit, tubes containing whole blood are centrifuged for 5 min at 10-12000 g to separate the whole blood into red cells and plasma. The hematocrit is calculated from the length of the blood column, including the plasma, and the red cell column alone, measured with a millimeter rule.
The conventional methods for measuring these two important blood parameters require too much time and too much blood for many applications. In particular, there is a significant need for fast ESR (or other sedimentation rate measure) and HCT diagnostic with minimal sample volume, in particular for point of care diagnostics.
Known automated methods measure the cell-plasma interface of a blood sample while rotating a cartridge holding the blood to determine both parameters by dynamic measurements. See for example Shelat et al, Am J Clin Pathol 2008; 130:127-130. These methods require complex precision hardware, in particular optical microscopy, while measuring from rotating a device. This complexity and associated costs are today a significant limitation for wide spread use of fast ESR and HCT measurements with small sample volumes.
Different devices and methods are known for processing liquids by centrifugation, exploiting phenomena at microscopic scale, leading to automated analytical systems with applications in different fields, including in the medical diagnostics domain. For automated analytical systems, there is a need for different functional modules to be included in a cartridge operated by rotation, for example aliquoting, blood plasma separation, mixing and liquid routing. These functional modules may be arranged in such ways that they operate in sequence or in parallel so as to follow a pre-defined protocol for analytical purposes.
Known aliquoting functional modules operated by centrifugation typically operate on a short time scale (in the order of seconds) and this may be a limiting fact or for some applications, where one requires controlled aliquoting for a pre-defined time. Furthermore, existing aliquoting functional modules may require a significant space in the cartridge, with additional structures for proper operation.
Therefore, there is a need for simple sequential aliquoting functional modules, operated by centrifugation, wherein the operating timescale can be controlled.